Does statin (HMG-CoA reductase inhibitor) therapy cause insulin resistance in postmenopausal women?

From the Guidelines

Statin therapy is associated with a small but significant increase in the risk of insulin resistance and new-onset diabetes in postmenopausal women, but the cardiovascular benefits of statin therapy outweigh this risk. The evidence from the JUPITER trial, which included women taking rosuvastatin, showed a small but significant increase in HbA1c compared with placebo (HbA1c 5.9 vs 5.8, P = 0.001), as well as a greater risk of developing new diabetes (1.53 vs 1.03 per 100 person-years, respectively; HR = 1.49; 95% CI: 1.11–2.01; P = 0.008) compared with men 1. Key points to consider include:

• The absolute risk increase is relatively small, with one case of incident diabetes for every 1000 women taking statins per year 1
• The guidelines recommend screening for new-onset diabetes while on statin therapy, but also recognize that the ASCVD risk reduction benefit outweighs the excess potential risk of diabetes 1
• Regular monitoring of blood glucose levels, typically every 3-6 months, is recommended for postmenopausal women taking statins
• Lifestyle modifications, including regular exercise, maintaining a healthy weight, and following a balanced diet, can help mitigate potential insulin resistance effects while on statin therapy
• The mechanism of statin-induced insulin resistance appears to involve impaired insulin secretion and decreased glucose uptake in muscle tissue, although the exact mechanisms are not fully understood 1

From the Research

Statin Use and Insulin Resistance in Postmenopausal Women

• The relationship between statin use and insulin resistance in postmenopausal women has been investigated in several studies 2, 3, 4, 5, 6.
• A study published in 2024 found that statin use is associated with an increased risk of new-onset type 2 diabetes mellitus (T2DM) in postmenopausal women, with factors such as the type and dose of statin and baseline metabolic status influencing this association 3.
• Another study published in 2012 found that statin use was associated with an increased risk of diabetes mellitus (DM) in postmenopausal women, with a hazard ratio of 1.71 (95% CI, 1.61-1.83) 5.
• The Women's Health Initiative study found that insulin resistance, as measured by the homeostasis model assessment of insulin resistance (HOMA-IR), was associated with higher cancer-specific and all-cause mortality in postmenopausal women 6.
• While these studies suggest a link between statin use and insulin resistance in postmenopausal women, the evidence is not yet conclusive, and further research is needed to fully understand this relationship 2, 4.

Mechanisms and Risk Factors

• The mechanisms by which statins may contribute to insulin resistance are not fully understood, but may involve changes in lipid metabolism and inflammation 3.
• Risk factors for insulin resistance and T2DM in postmenopausal women, including obesity, physical inactivity, and family history of diabetes, may also play a role in the association between statin use and insulin resistance 5.
• The type and dose of statin used, as well as the individual's baseline metabolic status, may influence the risk of insulin resistance and T2DM 3.

Clinical Implications

• Postmenopausal women taking statins should be monitored for signs of insulin resistance and T2DM, including regular blood glucose and lipid profile checks 5.
• Healthcare providers should consider the potential risks and benefits of statin therapy in postmenopausal women, taking into account individual risk factors and medical history 2, 4.
• Further research is needed to determine the optimal strategies for preventing and managing insulin resistance and T2DM in postmenopausal women taking statins 3, 6.